Morita Akihiko, Nakayama Tomohiro, Soma Masayoshi, Mizutani Tomohiko
Division of Neurology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Am J Hypertens. 2007 May;20(5):527-32. doi: 10.1016/j.amjhyper.2006.06.008.
Calcitonin-related peptide alpha (CALCA) is a neuropeptide that is a very potent vasodilator. It has been reported that CALCA knockout mice have a significantly elevated systolic blood pressure (BP). The aims of this study were to discover novel polymorphisms or mutations in the 5' flanking region of the human CALCA gene in Japanese subjects and to assess the association between this gene and essential hypertension (EH).
Japanese patients with EH (50.1 +/- 6.6 years old, n = 274) and age-matched Japanese subjects without EH (51.1 +/- 6.6 years old, n = 225) were recruited. The 5' flanking region of the human CALCA gene was searched to identify novel polymorphisms in the 20 EH patients using polymerase chain reaction (PCR) and a direct sequencing method. These novel polymorphisms, as well as the known single nucleotide polymorphisms (SNPs), were used for genotyping.
We discovered a novel 2-bp microdeletion polymorphism in intron 1. The only three participants with 2-bp microdeletion polymorphism were found in the EH group. None of the subjects without EH had a 2-bp microdeletion polymorphism. The genotype and allele distribution of the 4 SNPs were not significantly different between the groups. All five polymorphisms were located in one haplotype block. The haplotype was constructed using, in order, rs1553005, 2-bp microdeletion polymorphism, and rs5241. There was a significant association between EH and the C-AGins-A haplotype (P = .00031).
A novel 2-bp microdeletion polymorphism was discovered in the CALCA gene. Based on the results of the haplotype-based case control study, the CALCA gene could be the susceptibility gene for EH.
降钙素相关肽α（CALCA）是一种神经肽，是非常有效的血管舒张剂。据报道，CALCA基因敲除小鼠的收缩压（BP）显著升高。本研究的目的是在日本受试者中发现人类CALCA基因5'侧翼区域的新多态性或突变，并评估该基因与原发性高血压（EH）之间的关联。
招募日本EH患者（年龄50.1±6.6岁，n = 274）和年龄匹配的无EH日本受试者（年龄51.1±6.6岁，n = 225）。使用聚合酶链反应（PCR）和直接测序方法在20例EH患者中搜索人类CALCA基因的5'侧翼区域，以鉴定新的多态性。这些新的多态性以及已知的单核苷酸多态性（SNP）用于基因分型。
我们在内含子1中发现了一种新的2-bp微缺失多态性。仅在EH组中发现了三名具有2-bp微缺失多态性的参与者。无EH的受试者均无2-bp微缺失多态性。两组之间4个SNP的基因型和等位基因分布无显著差异。所有5种多态性均位于一个单倍型块中。按顺序使用rs1553005、2-bp微缺失多态性和rs5241构建单倍型。EH与C-AGins-A单倍型之间存在显著关联（P = .00031）。
在CALCA基因中发现了一种新的2-bp微缺失多态性。基于单倍型病例对照研究的结果，CALCA基因可能是EH的易感基因。
